Gene Expression Changes in Cultured Reactive Rat Astrocyte Models and Comparison to Device-Associated Effects in the...

Area of Science:

• Neuroscience
• Biomaterials Science
• Genomics

Background:

• Implanted neurotechnology shows therapeutic promise but faces challenges from the foreign body response.
• Astrocytes, key cells in central nervous system (CNS) damage, exhibit a spectrum of reactive phenotypes.
• Understanding reactive astrocyte subtypes is crucial for improving long-term device performance.

Approach:

• RNA sequencing was used to analyze transcriptomic profiles of two reactive astrocyte culture models (cytokine cocktail and lipopolysaccharide).
• Spatial transcriptomics compared in vitro models to gene expression surrounding implanted electrodes in rat motor cortex at various time points and distances.
• Immunohistochemistry identified glial fibrillary acidic protein (GFAP)-expressing astrocytes, and a factorization approach assessed reactivity marker relationships.

Key Points:

• Overlapping gene expression (up to ~250 genes) was found between in vitro models and in vivo responses, varying with implantation duration.
• Cytokine-induced astrocytes shared more genes with chronically implanted tissue (≥1 week) than LPS-exposed cells.
• Specific genes (e.g., Serping1, Chi3l1, Cyp7b1) showed localized expression in GFAP-expressing astrocytes near implanted devices.

Conclusions:

• Comparing reactive astrocyte culture models with spatial transcriptomics data can identify novel biomarkers for the foreign body response to neurotechnology.
• This approach offers a strategy for evaluating and developing in vitro models that accurately mimic tissue responses to implanted electrodes.
• Findings contribute to optimizing the design and efficacy of implantable neurodevices for treating neurodegenerative diseases.